Endocrine Abstracts

The orphan nuclear receptor, SF-1, is sumoylated in adrenal and gonadal tissues, but the role of sumoylation in pituitary gonadotrophs is currently unknown. We performed expression studies for key components of sumoylation machinery in αT3-1 and LβT2 gonadotroph cell lines, using RT-PCR. Expression of the genes encoding the SUMO proteins (Sumo1, Sumo2, Sumo3) as well as the E3 ligase enzymes responsible for their covalent linkage (Pias1, Pias2/xα, Pias...

Background: Russell–Silver syndrome (RSS) is a heterogeneous condition characterised by pre- and post-natal growth retardation in association with variable dysmorphic features including triangular facies and body asymmetry. The condition has previously been linked to 2 genetic abnormalities: aberrant methylation at the 11p15.5 locus in 30–40% and maternal uniparental disomy (UPD) of chromosome 7 in 10% of cases. Up to 50% of children currently have no identified (epi...

Growth hormone insensitivity, also known as Laron Syndrome (LS), is caused by mutations within the GH receptor (GHR). A 1.5 year-old boy with consanguineous parents was referred with postnatal linear growth failure (length 64 cms, minus 6 SDS). Facial features were typical of LS. Investigation revealed elevated serum GH (1145 mIU per litre) and low IGF-I (4 nmol per litre). Genomic DNA was isolated from peripheral blood leucocytes and all GHR exons, including intron-exon bound...

The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor by inactivating cortisol. Evidence suggests impaired 11beta-HSD2 activity in some patients with hypertension but also in patients with renal disease where it may contribute to sodium retention, oedema and hypertension. To date these studies have relied upon urinary cortisol metabolite analyses as markers of renal 11beta-HSD2 activity.We have directly a...

BackgroundPropylthiouracil treatment of Graves' disease has been postulated to provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, particularly myeloperoxidase (MPO)-ANCA, however it is unclear whether the abnormal immune environment of autoimmine thyroid disease influences the development of ANCA.MethodsThe occurrence of ANCA and the relationship to thionamide treatment was investigated in 407 patients' with Graves' disease, 200 with Hashimo...

Congenital isolated ACTH deficiency (IAD) is a rare inherited disorder that is clinically and genetically heterogeneous. Patients are characterised by low or absent cortisol production secondary to low plasma ACTH despite the absence of structural pituitary defects and normal secretory indices of other pituitary hormones. When tested, there is often no ACTH response to exogenous CRH. Onset may occur in the neonatal period, but often is first observed in later childhood. Candid...

Background: GH insensitivity (GHI) presents with growth failure, IGF-1 deficiency and normal/elevated GH (basal >5 μg/l and/or peak >10 μg/l). GHI encompasses a spectrum of clinical and biochemical abnormalities. Associations between phenotypic characteristics and genetic defects remain obscure.Objective: Identify phenotypic predictors of underlying genetic defects in GHI.Methods: In total of 102 children (62M) me...

Background: In children, Cushing’s disease (CD) presents with a combination of weight gain and slowed linear growth. First-line pituitary surgery is the treatment of choice for most patients. In paediatric patients, the transsphenoidal surgical success rate is 60%–98% when performed by an expert pituitary surgeon. There is a need for additional pharmacological interventions to control hypercortisolaemia, which are currently limited, in children and adolescents. In ph...

Introduction: Familial Partial Lipodystrophy Type 1 (FPLD1) is characterised by loss of gluteal and limb subcutaneous fat and increased abdominal fat. The genetic basis is currently unknown. FPLD1 is frequently associated with metabolic problems including diabetes, insulin resistance, dyslipidaemia and non-alcoholic fatty liver disease. Despite central adiposity and severe metabolic abnormalities, this group of patients often do not qualify for NHS funding for bariatric surger...

Background: Endogenous Cushing’s syndrome (CS) in children remains a challenge to diagnose and exclude. 24-h urinary free cortisol (UFC) measurements are a convenient, non-invasive test for paediatric patients.Objective: To assess the screening accuracy of 24-h UFC measurements in paediatric patients referred to our centre for evaluation of possible CS.Methods: A retrospective review of children referred to our centre between ...